Anticariogenic compositions comprising sodium pentafluorostannite,nasn2f5,and methods for utilizing same



United States Patent fiice ANTICARIOGENIC COMPOSITIONS COMPRISING SODIUM PENTAFLUOROSTANNITE, NaSn F AND METHODS FOR UTILIZING SAME Joseph C. Muhler, Indianapolis, Ind., assignor to Indiana University Foundation, Bloomington, Ind., 21 not-forprofit corporation of Indiana N Drawing. Continuation-impart of application Ser. N 0. 374,240, June 11, 1964. This application Feb. 8, 1968, Ser. No. 703,859

Int. Cl. A611; 27/00 U.S. Cl. 424131 9 Claims ABSTRACT OF THE DISCLOSURE CROSS REFERENCE This application is a continuation-in-part of applicants co-pending United States patent applica ion entitled Anticariogenic Compositions and Methods, Ser. No. 374,240, filed June 11, 1964, now abandoned.

BACKGROUND OF THE INVENTION Field of the invention This invention relates to a new composition of matter, sodium pentafluorostannite, NaSn F and to uses thereof as a systemically effective anticariogenic agent. Further, the invention relates to a novel technique for reducing caries by the ingestion of stannous-containing fluoride salts, including the novel sodium pentafluorostannite disclosed herein, whereby systemic anticariogenic effects for the said salts may be obtained, both in treated recipients and, in the case of a pregnant female, in her ultimate offspring.

DESCRIPTION OF THE PRIOR ART It is commonly recognized that the presence of small amounts of fluoride in drinking water (e.g., 1.0 ,ug. F /ml.) has a significant effect in reducing the incidence of dental caries in permanent teeth of human children consuming such water from birth through eight years of age. Soluble fluoride salts have been introduced into public Water supplies in a number of communities with good results. This method of providing fluorine is not feasible, however, where drinking water is obtained from small, private fluoride-deficient sources such as individual Wells, etc., rather than from fluoridated (naturally or fortified) common public sources. Further, the addition of fluorine to common public sources is not always accepted or permitted.

Topical application of aqeuous fluoride solutions by a dentist or dental hygienist provides an excellent measure of protection against caries. Various fluoride compounds 3,492,401 Patented Jan. 27, 1970 have been employed in this manner, including sodium fluoride and stannous fluoride. Such topical treatments, although relatively effective, are expensive and extremely time consuming for both the profession and patient and thus are not always available to persons desiring them.

Limitations on the availability of fluoride prophylaxis by way of water supplies or the dental oflice have lead to extensive efforts to incorporate various fluoride salts in oral compositions for use in the home, most practicably obtained in the form of fluoride dentifrices. Although an effective toothpaste containing stannous fluoride as the anticariogenic agent and calcium pyrophosphate as the abrasive is commercially available, dental researchers have continued their efforts to find more effective anticariogenic agents and more effective manners for utilizing these agents in preventive dentistry.

SUMMARY OF THE INVENTION In accordance with the present invention, novel anticariogenic compositions comprising anticariogenically effective and non-toxic amounts of sodium pentafluorostannite, NaSn F have been developed. Such compositions have been found to exhibit systemic anticariogenic activity after oral ingestion thereof. Moreover, the sodium pentafluorostannite-containing compositions have been found to exert a placental transferring ability (even in the presence of calcium salts), so that dietary supplements having such stannous-containing fluoride salts formulated therein may be effectively utilized for a systemic anticariogenic effect on ultimate offspring of the recipient of the supplements. Compositions in accordance with the present invention preferably comprise about 1.9l5.0 milligrams of NaSn F (i.e., at a level sufficient to supply about 0.5 4.0 milligrams fluoride ion). The preferred NaSn F level is about 3.7 milligrams (1.0 mg. fluoride ion).

Accordingly, it is a primary object of this invention to provide compositions comprising an anticariogenic and nontoxic amount of sodium pentafluorostannite and which are adapted for oral ingestion and systemic anticariogenic eflicacy.

Another object of this invention is to provide a dietary supplement composition comprising NaSn F and having systemic anticariogenic eflicacy, both in the recipient thereof and, in the case of pregnant female recipients, in her ultimate offspring.

It is a still further object of this invention to provide new methods for reducing the incidence of dental caries in humans.

These and other objects, advantages, and features of the subject invention will hereinafter appear, and, for purposes of illustration, but not of limitation, various exemplary embodiments of the subject invention are hereinafter described in detail.

DESCRIPTION OF THE PREFERRED EMBODIMENTS In accordance with the subject invention,-it has been found that a systemically effective anticariogenic agent may comprise an anticariogenically effective and non-toxic amount of sodium pentafluorostannite, NaSn F More particularly, compositions in accordance with the present invention comprise about 1.9 up to about 15.0 milligrams NaSn F (about 0.5-4.0 milligrams calculated as fluoride ion). Optimal compositions comprise about 3.7 milligrams NaSn F (1.0 milligram calculated as fluoride ion). As will hereinafter be described in detail, such compositions are systemically effective on both a preand post-natal basis in humans. Where used post-natally, such compositions should comprise about 1.9 milligrams NaSn F (0.5 milligram, calculated as fluoride ion) up to age three, and 3.7 milligrams NaSn F thereafter (1.0 milligram calculated as fluoride ion).

The formulation and characteristics of sodium pentafluorostannite, NaSn F are set forth in detail in applicants co-pending divisional application, Ser. No. 652,642, filed May 22, 1967.

Compositions in accordance with the present invention may be in solid dosage unit form (e.g., capsules or tablets) or they may be formulated in liquid form. Usually, the NaSn F is provided with a suitable amount (e.g., several hundred milligrams) of a non-toxic, physiologically inert carrier. Suitable carriers include polyhydric alcohols (e.g., sorbitol, mannitol, polyethylene glycol, glycerol or glycerin, prophylene glyco, and the like); fatty acids (e.g., oleic, palmitic or stearic acid, and the like); esters of sorbitan (e.g., products commercially available under the trademarks Tween 80 and Tween 20"); natural and synthetic binders (e.g., gum tragacanth, acacia, agar, gelatin, carboxymethyl cellulose, hydroxyethyl cellulose, and the like); fatty acid salts (e.g., magnesium stearate and the like); inert silicates (e.g., kaolin, talc, and the like); starches and saccharides (e.g., lactose and the like); and mixtures thereof. The exact amount of the carrier is of course not critical as it merely serves to provide the agent in a dosage form suitable for convenient human consumption.

Alternatively, or additionally, such anticariogenic composition may further serve as a dietary supplement comprising vitamins and/or minerals in suitable amounts and proportions (e.g., at minimum daily requirement levels) as are well known to those skilled in the art.

Pre-natal products in accordance with the present invention advantageously comprise one or more calcium salts in amounts lying between about 100400 milligrams, and, preferably, about 200300 milligrams, calculated as calcium ion. The optimal calcium level is about 250 milli grams, calculated as calcium ion. Suitable non-toxic calcium salts include calcium carbonate (CaCO calcium gluconate (C H O Ca-H O); calcium glycerophosphate (C H O CaP); calcium lactate (C H O Ca); calcium phosphate, monobasic [Ca(H PO -H O]; calcium phosphate, dibasic (Cal-IP calcium phosphate, tribasic [Ca (PO calcium propionate (C H O Ca); calcium pyrophosphate (Ca P and calcium tartrate Exemplary compositions in accordance with the present invention are set forth in the following examples. In addition to the constituents set forth in the following examples will of course contain minor amounts of excipients for manufacturing and consumer acceptance purposes. Suitable excipients include hydroxyethyl cellulose, magnesium stearate, acacia, gelatin, Kaolin, sodium saccharin, and artificial color, fiavorings and the like.

Examples I and II are pre-natal vitamin-mineral tablets or capsules comprising NaSn F at a level of 1.0 milli- 4 EXAMPLE H Sodium pentafluorostannite mg 3.74 Vitamin A (acetate or palmitate) I.U. 4000 Vitmain D I.U. 400 Vitamin C mg- 75 Vitamin B mg 3 Vitamin B mg 2 Vitamin B mg 10 Vitamin B mg 5 Vitamin B ug 3 Iron mg 40 Calcium (lactate as calcium ion) mg 250 Examples III and IV are post-natal, chewable vitamin tablets comprising sodium pentafluorostannite.

EXAMPLE =III Sodium pentafluorostannite mg 1.87 Vitamin A LU.-- 4000 Vitamin C mg 75 Vitamin D (calciferol) I.U. 400 Vitamin B mg 1.0 Vitamin B mg 1.5 Vitamin B mg 10.0 Vitamin B mg 1.0 Vitamin B mg 1.5 Mannitol mg 363.4 Starch mg 28.0 Saccharin soluble mg 1.0 Acacia mg 7.0 Flavor mg 3.0 Magnesium stearate mg 6.0 FD & C color ,agn. 8.0

1 International units.

EXAMPLE IV Sodium pentafiuorostannite mg 3.74 Vitamin A I.U. 4000 Vitamin C mg 75 Vitamin D I.U. 400 Vitamin B mg 1.0 Vitamin B mg 1.5 Vitamin B mg 10.0 Vitamin B mg 1.0 Vitamin B12 pg 1.5 Mannitol mg 361.5 Starch m 28.0 Saccharin soluble mg 1.0 Acacia mg 7.0 Flavor mg 3.0 Magnesium stearate mg 6.0 FD & C color /.g 8.0

Example V is a suitable pre-natal non-vitamin NaSn F preparation and Examples VI and VII are post-natal nonvrtamin NaSn F preparations.

EXAMPLE V Sodium pentafluorostannite mg 3.74 Lactose mg 186.47 Starch mg 26.00 Acacia mg 6.50 Saccharin sodium mg 0.40 Magnesium stearate mg 2.50 FD & C Red #2 and #3 (coloring) ,ug 42.

EXAMPLE VI Sodium pentafluorostannite mg 1.87 Mannitol mg 451.93 Starch mg 28.0 Saccharin soluble mg 1 0 Acacia mg 7 0 Tartaric acid mg 1.2 Flavor mg 3.0 Magnesium stearate mg 6 0 PD 5; C co or H" flqunnhuv gu 8.0

EXAMPLE VII Sodium pentafluorostannite mg 3.74 Mannitol mg 450.06 Starch mg 28.0 Saccharin soluble mg 1.0 Acacia mg 7.0 Tartaric acid mg 1.2 Flavor mg 3.0 Magnesium stearate mg 6.0 FD & C color g" 8.0

Example VIII gives the composition of a 0.6 cc. dose of a liquid NaSn F -vitamin preparation. A dosage of 0.6 cc./day yields the required minimum level of NaSn F (0.5 milligram calculated as fluoride ion).

EXAMPLE VIII Sodium pentafluorostannite mg 1.87 Vitamin A I.U 3000 Vitamin D I.U 400 Vitamin C mg 60 The balance of the formulation consists of sorbitol, water, Tween 80, and artificial sweetening agents, flavors, and color.

Example IX gives the composition of a 1.0 cc. daily dose which provides NaSn F at a level of 0.5 milligram, calculated as fluoride ion.

It should be understood that the constituents of the foregoing preparations other than NaSn E= are conventional as are the amounts and proportions thereof except, however, that as hereinafter set forth in detail, it has been unexpectedly discovered that the utilization of calcium salts in these preparations does not adversely effect the anticariogenic activity of the preparations.

TABLE I.DENTAL CARIES DATA FOLLOWING inhalation, and the heads were removed, coded, and examined for dental caries by conventional techniques (as described by Muhler et al., Studies on Stannous Fluoride and Other Fluorides in Relation to the Solubility of Enamel in Acid and the Prevention of Experimental Dental Caries, J. Dent. Res, 33 :33, 1954).

The dental caries data for the three groups are shown in Table I. The control animals were found to have an average of 6.70 carious lesions, while the animals which received 1.0 mg. of fluoride as NaF daily by stomach tube were found to have an average of 4.51 carious lesions and the animals which received an identical amount of fluoride as NaSn F were found to have an average of 3.69 carious lesions. As shown in Table I, this finding represents a mean percent reduction in carious lesions of 32.7% and 44.9% for NaF and NaSn F respectively demonstrating a significantly (p:0.001) greater effectiveness with the use of NaSn F The average severity of the individual lesions was quite comparable in the three groups, but, when severity was evaluated in terms of the amount of tooth substance actually afllicted by caries, values of 30.8, 18.9, and 16.0 were obtained in Groups 1, 2, and 3 respectively.

The general findings observed in the incidence of dental caries are reflected in the data relative to the amount of tooth substance afiiicted with caries. The control animals were found to have a mean carious area rating of 30.8, while values of 18.9 and 16.0 were found in Groups 2 and 3, representing significant (p=0.001) reductions of 38.6 and 48.1 percent, as compared to the values found in the control animals. Once again a significantly greater (p-=0.001) effectiveness in reducing dental caries was seen with the use of NaSn F One possible explanation for the greater effectiveness of NaSn F in reducing dental caries in rats is the fact that the presence of tin with fluoride apparently imparts a greater anticariogenic potential than fluoride alone. At any rate, regardless of the possible explanation, the reported caries data indicate that significant reductions can be obtained in both caries incidence and Severity with both NaF and NaSn F and that a significantly greater effectiveness can be attributed to NaSn F as compared to NaF.

SYSTEMIC ADMINISTRATION OF NaF AND NaSa2F Mean Mean Mean Mean Cartons Percent No. Percent Moan Area Red. in Group Regimen Lesions Red. t p Severity Score Area I; p Dist. H O *6.70:l:0.45 t 2- 10 30.8:l:2.5 11F 4. 51:1;0. 51 32. 7 14. 411 0. 001 1. 99 1S. 9:1:2. 5 38. 6 15. 113 0. 001 3 NaSn F 3. 69i0. 44. 9 20. 743 0.001 2.02 10. 0i2. 5 48. 1 18. 189 0, 001

POST-NATAL SYSTEMIC ANTICARIOGENIC EFFECTIVENESS OF NaSn F The post-natal systemic anticariogenic effectiveness of NaSn F can be demonstrated by the dental caries experience of rats (standard experimental animals for anticariogenic studies) treated with fluoridated drinking water on a comparative controlled diet study, as in the following manner.

A total of 153 weanling male rats were divided equally into three groups (1, 2, and 3) according to body weight. The animals were housed in wire cages in an air-conditioned room and were provided distilled water ad libitum. They were maintained on a low-fluoride stock corn diet for nine days prior to initiating the study and for ten days after the study was begun. The composition of the stock corn diet was as follows (in percent): yellow corn meal, 64.0; powdered whole milk, 30.0; alfalfameal, 4.8; iodized salt, 1.0; and irradiated yeast, 0.2.

During the experimental period, each group of animals was given the following solutions daily by stomach tube: Group 1, 1.0 ml. distilled water; Group 2, 1.0 mg. fluoride as NaF in 1.0 ml. water; and Group 3, 1.0 mg. fluoride as NaSn F in 1.0 ml. water. At the end of the experimental period, the animals were sacrificed by chloroform The forgoing animal studies have been confirmed. in a human clinical study. A group of children between the ages of 2 and 3, residing in non-fluoride areas were given a thorough dental caries examination with the aid of bitewing radiographs. This group was then divided into two sub-groups according to dental ages and past dental experience. Each day the members of Group 1 (control) were given a chewable vitamin table and Group 2 received a chewable tablet containing the same vitamins, and additionally 1.0 mg. of F as NaSn F Both groups were given thorough dental examinations six months and twelve months after the test was begun.

Table II reports the results of these tests in terms of deft (decayed, exfoliated, and filled deciduous teeth) and defs (decayed, exfoliated, and filled deciduous surfaces). The data reported in Table II demonstrate the high level of effectiveness in the reduction of dental caries of the NaSn F comprising the present invention. In particular, after six months a mean percentage reduction of 46.0 and 49.8 in the incidence of deft and defs respectively, was found in Group 2 as compared with Group 1 (control). In the examinations conducted after twelve months the corresponding figures Were 65% and 71.2%. No deleterious effect due to the use of the subject invention could be found. Thus, the study reported in Table II verifies and confirms the post-natal (i.e., pediatric) utility of NaSn F as a systemic anticariogenic agent.

8 At the birth of the pups all of the mothers and their litters were placed on distilled water and a corn-sucrose cariogenic diet. The composition of the corn-suc ose cario- TABLE II.SUMMARY OF PRELIMINARY CLINICAL FINDINGS AFTER SIX AND TWELVE MONTHS Mean Mean Mean Mean Number Initial Initial deft Percent deft percent Group subjects Regimen deft deft increment reduction increment reduction G-MONIH DATA 1 46 Control 1. 28 1. 63 1. 63 2. 35 2 33 Nasn F 1. 57 2. 0. 88 46. 0 1. 18 49. 8 IQ-MONTH DATA 1 31 Control 1. 13 1. 39 27 74 5. 20 2 24 NaSmF 1. 66 2.21 0. 96 65. O 1.50 71. 2 PRE-NATAL UTILIZATION OF NaSn F AND genie diet was as follows (in percent): yellow corn grits,

OTHER STANNOUS-CONTAINING FLUORIDE SALTS The foregoing enamel solubility and dental caries studies exemplify the anticariogenic potential of the novel NaSn F as asystemically effective anticariogenic agent in an orally ingested composition. However, in another of its aspects, the present invention embraces the use of NaSn- F with particular regard to the pre-natal treatment of pregnant human females in order to impart a lessened tendency for caries incidence in the deciduous teeth of the ultimate offspring.

It has not heretofore been recognized that certain fluoride salts have the ability to pass the placenta in order to partake in the embryonic development of the ultimate offspring and thereby to render the deciduous teeth of such offspring less susceptible to caries incidence. This placental passing nature of the fluoride salts described herein suggests the use of such salts a component of dietary supplements for pregnant females (e.g., vitamin and mineral supplements). However, it is well known that pregnant females are desirably maintained on a high calcium diet (e.g., commercial pro-natal dietary supplements contain a substantial amount of calcium salts), and therefore an essential requisite of an eflective pre-natal anticariogenic technique would be the compatibility of the anticariogenic placenta passing agent with ionic calcium.

An important aspect of the present invention resides in the discovery that the ability of NaF to pass the placenta is significantly retarded by the presence of ionic calcium, while the ability of sodium pentafluorostannite disclosed herein to similarly pass the placenta is substantially unimpaired by the corresponding presence of ionic calcium.

TABLE III.-WEIGHT GAIN 46.0; powdered whole milk, 28.5; sucrose, 19.5; alfalfa meal, 4.8; iodized salt, 1.0; and irradiated yeast, 0.2. The pups were maintained on this regimen for a period of eight weeks after birth. At the end of this period, they were sacrificed by chloroform inhalation, and the heads were removed, coded, and scored for caries according to conventional methods (described in Muhler et al. op. cit., J. Dent. Res, 33, 33, 1954).

The data obtained are shown in Table III. The control males were found to have an average of 11.00 carious lesions while a value of 9.94 was found for the females. The animals whose mothers had received 100 ppm. fluoride as NaF during the pre-natal period were found to have an average of 12.89 and 11.21 lesions for males and females, respectively. When SnF was provided to the mothers during the prenatal development, caries scores of 6.73 and 7.14 were found in the males and females, respectively, representing reductions of 38.8 and 28.2 percent when compared to the controls. When NaSn F was provided as the pro-natal fluoride, even greater reductions were obtained in the males with a 57.0 percent reduction in caries while a 43.7 percent reduction was obtained in the females.

The caries severity values as well as the carious area severity values, which consider the average depth of the lesion and the average involved area res ectively, tend to show the same general trends as shown by the number of carious lesions, although more pronounced differences are seen when the total involved area is considered. The growth data (which are also shown in Table III) indicate that pre-natal fluoride administration had no apparent effect upon the average weight gain. In fact, numerically greater Weight gains occurred in many of the prenatal fluoride groups as compared to that of the controls.

AND CARIES DATA IN OFFSPRING OF RATS WHICH RECEIVED 100 P.I.M. FLUO- RIDE IN THE DRINKING WATER ONLY DURING THE PRE-NATAL PERIOD Mean M gerctent 4 ean area re Pre-natal Final No. Mean final Mean No. percent Mean severity ril d-Z Group regimen Sex animals weight (g.-) lesions reduction severity score severity 1 Distilled water.-- M 13 77. 15:24. 0 11. 00:1:3. 5s 0 2. 32 63. 83:25. 2 0 F 16 69. 43:24. 9 9. 94:1:3. 34 0 2. 28 55. 6:1:25. 7 0 NaF M 9 78. 95:12. 0 12. 893:5. 23 +17. 2 2. 15 63. 2:33. 9 0. 9 F 14 75. 6:1;15. 3 11. 215:2. 61 +12. 8 2. 34 6525:23 1 +17. 3 3 M 11 77. e117. 7 6. 73:1:3. 52 3s. a 2.38 41. 15:21. 5 35. 6 F 14 87. 5:1:25. 1 '7. 14:51.63 28. 2 2. 21 37. 5:1;22. 7 32. 6 A. NasngF M 14 87. 6:1:32. 5 4.73:1:2. 54 5?. 0 1. 92 13. Till. e 70. 7 F 12 89. 35:19. 7 5. 6013. 78 43. 7 2. 02 24. 7:1; 18. 8 55. 6

A comparative study of a variety of fluoride compounds was undertaken to determine the ability of the compounds to provide fluoride to a developing placenta and to evaluate the effect of placentally-transfelred fluoride upon the future caries experience of the offspring.

A total of sixty young adult female Wistar rats were divided into four equal groups. The animals were mated and maintained on a low fluoride stock corn diet comprising (in percent): yellow corn meal, 64.0; powdered whole milk, 30.0; alfalfa meal, 4.3; iodized salt, 1.0; and irradiated yeast, 0.2. The various fluorides were provided in the drinking water as follows: Group 1, distilled water (control); Group 2, NaF; Group 3, SnF and Group 4, NaSn F All the fluorides were added at a concentration of 100 p-p-in, fl o de and were p p ed fresh ly- The foregoing data clearly indicate that the administra tion of pro-natal fluorides to rats can serve to significantly alter the dental caries experience in the offspring. The data further indicate that this effect is a function of the fluoride compound being administered, since NaF failed to produce any beneficial effect, while the same level of fluoride in the form of NaSn F produced a protection against dental caries. While the data suggest that the presence of the stannous ion is required along with the fluoride ion to produce a beneficial effect, it is apparent that the structure of the stannous-containing fluoride salt is of great importance since SnF was only about as worth-while as NaSn F The pre-natal utility of the NaSn F compositions of the present invention have been confirmed by human clinical data. In the human evaluations, three groups of mothers (Groups 1, 2, and 3) were supplied daily tablets containing 1 mg. F (as NaSn F 1 mg. F (as NaF), and 1 mg. Cl (as NaCl), as control, respectively, with the remaining pill bulk constituting mannitol, a conventional carrier which is not metabolized in the oral cavity. All mothers commenced ingestion of the pills within three months of conception and continued daily ingestions until parturation. The three year caries history of the resultant children are expressed in Table IV in terms of deft (decayed, exfoliated (and filled deciduous teeth) and defs (decayed, exfoliated, and filled deciduous surfaces).

It is apparent from these results that pre-natal NaF provides no significant caries control for ultimate offspring, while pre-natal NaSn F significantly reduces caries susceptibility in the offspring. This phenomenon can be explained only by the unique ability of the stannouscontaining fluoride salt (i.e., in this study, NaSn F to pass through the placenta and to affect the formation of the offsprings teeth in a manner that yields improved oral hygiene even up to three years after birth.

10 thirty days. At the end of the thirty day interval, the animals were sacrificed by chloroform inhalation, and the pelts and both femurs were removed. The carcasses and the femurs were separately ashed and analyzed for fluoride.

The results obtained from the fluoride analyses of the carcasses are summarized in Table V. The results obtained from the femur fluoride analyses are also shown in Table V, and these data tend to reflect the findings noted in the whole carcasses. The data of Table V reveal that the effect of added dietary calcium upon the retention of fluoride administered as NaF is very pronounced. The addition of 0.5 percent calcium as calcium carbonate (Group C) reduced the carcass fluoride retention by 10.1 percent, this value being significant at the 0.001 level. When calcium lactate was added to the diet as the source of calcium, the retention of fluoride as NaF was again significantly (p=0.001) decreased by 15.1 percent, as compared to the respective control value obtained in Group B. Even more pronounced decreases were found When the calcium was added as the phosphate salts (Groups E and F). Here highly significant (p=0.001)

TABLE IV.PRE-NATAL HUMAN CLINICAL STUDIES Three year data No. N 0. Percent Percent Group Regimen mothers children Deft Red. Defs Red. 1 NELSDQF5 56 61 3. 61 40. 8 4. 88 51. 6 2 NaF 56 6. 08 0. 3 9. 75 0.3 3 NaCl (control) e, 49 45 6. 10 10. 10

CALCIUM ION COMPATABILITY OF PRE-NATAL FLUORIDES As previously indicated, the compatibility of the placenta-passing fluoride salt with ionic calcium is an important consideration in determining the practical effectiveness of such a salt for use in a pre-natal dietary supplement technique. The following studies demonstrate the effect of the presence of ionic calcium on the carcass and femur retention of fluoride from NaF and NaSn F A total of 110 weanling female Wistar rats were divided into eleven equal groups according to body weight. All animals were housed in wire screen cages in an air-conditioned room and received distilled water ad libitum. The animals were provided with one of the following diets ad libitum: Groups A, B, and G, a low fluoride stock diet, the composition of which was as follows (in percent): yellow corn meal, 64.0; powdered whole milk, 30.0; alfalfa meal, 2.8; iodized salt, 1.0; and irradiated yeast, 2.0; Groups C and H, a diet containing added 0.4 percent calcium as calcium carbonate added at the expense of corn meal; Groups D and I, a diet containing 0.5 percent added calcium as calcium lactate; Groups E and J, a diet containing 0.5 percent added calcium as monobasic calcium phosphate; and Groups F and K, a diet containing 0.5 percent added calcium as dibasic calcium phosphate. In addition, the animals in Groups B through F received 1.0 mg. fluoride as NaF daily by stomach tube, while the animals in Groups G through K received the same amount of fluoride in a similar manner as NaSn F The animals were maintained on these respective regimens for TABLE V.CARCASS AND FEMUR FLUORIDE DATA IN THE PRESENCE decreases in fluoride retention of 17.5 and 19.1 percent were found.

The effects of identical dietary calcium levels upon the retention of fluoride administered as NaSn F are in contrast to those obtained when NaF was used as a source of fluoride. The addition of 0.5 percent calcium to the diet resulted in no significant changes in the retention of fluoride in the whole carcass as compared to the amount retained in the absence of added dietary calcium. This effect was noted in all four groups which received added dietary calcium, with the solubility and physical properties of the particular calcium salt employed as a source of calcium having no detectable effect upon the retention of fluoride.

The results obtained in the femur analysis quite closely parallel the findings obtained in the analyses of the whole carcass. Again, the addition of dietary calcium significantly (p=0.001) decreased the skeletal retention of fluoride administered as NaF. When NaSn F was used as a source of fluoride, none of the calcium-enriched diets were found to appreciably alter the retention of fluoride.

In confirmation of these data, additional studies have shown that the rate of fluoride absorption in rats was decreased when ionic calcium was present and NaF was used as a source of fluoride. In contrast, when NaSn F was employed as a source of fluoride, the rate of fluoride absorption was increased by the presence of ionic calcium. No explanation of these findings is readily apparent, but these data clearly indicate the specificity involved in the use of different fluoride compounds in th presence of different sources of calcium.

AND ABSENCE OF ADDED DIETARY CALCIUM Supplemental ions Carcass data Filter data N et Percent F (1,0 Mean ash Mean, Mean ash Mean, Mean percent Change Group mg./da.) Calcium (0.5%) wt. (g.) p.p.n1. F Mean g. F. Wt. (1I1g.) p.p.n1. F g. F F. Ret. Due to 0a A 434550143 213. 83:12. 6 1 932. 71:52. 7 291. 5112. 2 261. 4158.1 1 75. 3 5, 0 B. NaF 4. 399510. 160 4,001i1s1 17, 850:|=440 293.5i14.8 5,979 316 1, 740 60 96 c NaF CaCO; 4. ssoio. 007 3, 530:1;127 16,050i410 202. 018.2 4, 858:1:180 1, 410550 54. 86 -11.5 D Cacti-1100551120 3. 842:1:0. 146 3, 969:1;176 15, 160i670 250. 9:1;10. 9 5, 51951268 1, 370:1;70 51. 76 -16. 5 E ca H2Po, 2H2 4.812;!z0. 121 3, 075:1:124 14, 720i480 343.3;tl3.7 4, 241:|:139 1, 4505150 50.56 -1s.4 F CaHP 5 113110. 06 21839191 1 24401600 358.5i10.8 3, 9905:15 1 1, 430i60 40. 56 20.0 G 3 816510. 21 4, 331:1;200 16, 1605340 237. :14. 7 6, 5465;379 1, 5105 1511 55 5 H CO 3. 940i0. 104 4, 1001158 16, 260:1:390 258. 93:15. 7 6, 2071216 1, 590:f:70 56. 16 +1. 1 CaCeHs5Hz 3. TOGi-O. 078 4,18%;65 15, 4805:1380 24s. 5i8. 4 5, 985:1;140 1, 400is0 53.23 -4. 2 J Ca(H2PO4)2H2O 3. 7201110. 157 4, 5553:225 16, 570:1:460 252. 15:13. 1 6, 403:]:299 1, 590:1;70 57. 20 +3, K NaSnzF5 CaHPO; 4.221:1=0.211 3,9861175 16, 7301-410 279. 8:1;110 55311240 1, 520i50 57.50 +3.5

1 Standard deviation of the mean.

2 Obtained by combining carcass and femur values and subracting the respective control values.

Thus, it will be seen that the present invention includes not only novel anticariogenic compositions comprising NaSn F but also novel methods for reducing the incidence of dental caries in humans on both a pre-natal and a post-natal (i.e., pediatric) basis.

It should be understood that various changes and modifications may be eifected in the details of formulation and the manner of application of the various exemplary embodiments described herein, without departing from the spirit and the scope of the instant invention, as defined in the appended claims.

1. An anticariogenic composition adapted for oral ingestion comprising about 1.9-150 milligrams sodium pentafiuorostannite, NaSn F 2. A composition, as claimed in claim 1, which comprises about 37 milligrams of sodium pentafiuorostannite, NaSn F 3. In a composition comprising a non-toxic calcium ion containing salt, the improvement comprising sodium pentafluorostannite, NaSn F being present in the composition at a level of about 1.915.0 milligrams.

4. An anticariogenic composition adapted for oral ingestion comprising about 1.9-15.0 milligrams of sodium pentafluorostannite, NaSn F and about 100-400 milligrams, calculated as calcium ion, of a member selected from the group consisting of calcium carbonate (CaCO calcium gluconate (C H O Ca-H O); calcium glycerophosphate (C H O CaP); calcium lactate (C H O Ca); calcium phosphate, monobasic [Ca(H PO -H O]; calcium phosphate, dibasic (CaHPO calcium phosphate, tribasic Ca (PO calcium propionate (C H O Ca); calcium pyrophosphate (Ca P O and calcium tartrate (C-aC H O 4H O 5. A method for reducing the incidence of dental caries in humans comprising the step of ingesting an anticariogenic composition comprising about l.915.0 milligrams of sodium pentafluorostannite, NaSn F 6. A method for reducing the dental caries susceptibility of human ofispring comprising the step of orally administering to the female parent thereof during the pre-natal period an anticariogenic composition comprising about 1.915.0 milligrams sodium pentafiuorostannite, NaSn F 7. A method, as claimed in claim 6, wherein the composition comprises about 3.7 milligrams of sodium pentafluorostannite, NaSn F 8. In a method comprising the step of orally administering a composition comprising a non-toxic calcium ion containing salt to the human female parent during the pre-natal period, the improvement comprising providing about 1.9-15 .0 milligrams of sodium pentafiuorostannite, NaSn F in the composition in order to reduce the dental caries susceptibility of the offspring thereof.

9. A method for reducing the dental caries susceptibility of human oflspring comprising the step of orally administering to the female parent thereof during the pre-natal period an anticariogenic composition comprising about l.9-lS.0 milligrams of sodium pentafiuorostannite, NaSn F and about -400 milligrams, calculated as calcium ion, of a member selected from the group consisting of calcium carbonate (CaCO calcium gluconate (C H O Ca H O) calcium glycerophosphate calcium lactate (C H O Ca); calcium phosphate, monobasic [Ca(H PO -H O]; calcium phosphate, dibasic (CaHPO calcium phosphate, tribasic [Ca (PO.,) calcium propionate (C H O Ca); calcium pyrophosphate (Ca P O and calcium tartrate (CaC I-l O -4H O).

References Cited UNITED STATES PATENTS 3,070,510 12/1962 Cooley et al. 42452 OTHER REFERENCES American Drug Index, 1963, published by I. B. Lippincott Co., Phila, p. 149.

Journal of Dental Research, vol. 40, No. 4, July-August 1961, p. 725.

McDonald et al., Acta. Cryst., vol. 17, pp. 1104-1108, September 1964.

Schaap et al., J. Amer. Chem. Soc., vol. 76, pp. 5226- 5228, 1954.

RICHARD L. HUFF, Primary Examiner 

